Coincident myelodysplastic syndrome and T‐cell large granular lymphocytic disease: clinical and pathophysiological features

Abstract

Myelodysplastic syndrome (MDS) and T‐cell large granular lymphocytic disease (T‐LGL) are bone marrow failure disorders. Successful use of immunosuppressive agents to treat cytopenia in MDS and LGL suggests a common pathophysiology for the two conditions. Of 100 patients with initial diagnoses of either MDS or T‐LGL referred to the National Institutes of Health for immunosuppressive treatment of cytopenia, nine had characteristics of both T‐LGL and MDS (T‐LGL/MDS). Fifteen patients with T‐LGL received cyclosporin (CSA) (10 responses). Eight out of nine patients with T‐LGL/MDS received CSA (two responses) and one patient received ATG (one response). Of 76 patients with MDS, eight received CSA (one response) and 68 received ATG (21 responses). The response to immunosuppression was significantly lower in patients with T‐LGL/MDS and MDS than in patients with T‐LGL disease alone (28% vs. 66%, P = 0·01). The proportion of T‐helper cells and T‐suppressor cells with an activated phenotype (HLA‐DR+) was increased in patients with T‐LGL, T‐LGL/MDS and MDS, but the increase in activated T‐suppressor cells in patients with T‐LGL/MDS was not statistically significant. Autoreactive T cells may suppress haematopoiesis and contribute to the cytopenia in T‐LGL and some patients with MDS, leading to T‐LGL/MDS. The lower response rate of MDS or T‐LGL/MDS to immunosuppression, compared with T‐LGL alone, may reflect the older age and intrinsic stem cell abnormalities in MDS and T‐LGL/MDS patients.

Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome

“…Variables previously linked to clinical response to immune suppression include bone marrow hypocellularity, presence of HLA-DR15 expression, younger age, lower platelet count, blast percentage and shorter duration of transfusion requirement, which are primarily features associated with favorable prognosis. 5,13,14,18,19,55,56 The presence of clonal T cells was not significantly associated with any of the clinical factors examined, although there was a slight positive trend with increasing IPSS risk category. Multivariable analyses were limited by small sample size, thus, our data do not preclude the possibility that multiple clinical factors combined may be more strongly associated with immunologic activation than any single factor.…”

“…[4][5][6][7][8][9][10][11][12] Univariant and multivariant statistical analyses have identified clinical and biological features associated with clinical response to immunosuppressive therapy, which served as the basis for the generation of response predictive models. [4][5][6][13][14][15][16][17][18] In these analyses, bone marrow hypocellularity, HLA-DR15 phenotype, younger age, lower platelet count and shorter duration of transfusion requirement were associated with response to immunosuppressive therapy. 5,14,19 Analogous to aplastic anemia, elimination of a hematopoietic suppressor T-cell population is hypothesized to underlie treatment response to immunosuppression in this subset of MDS patients.…”

Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes

“…26,28,[30][31][32][33][34][35][36][37][38][39] Although the presence of megakaryocyte or granulocyte dysplasia is a feature of MDS in a hypoplastic marrow (hypoplastic MDS), erythroid hyperplasia may also occur in aplastic anemia. 28 In aplastic anemia, pancytopenia is believed to be caused, at least in part, by T-cell-mediated progenitor cell inhibition, but susceptibility of hematopoiesis to attack by T cells may also exist in MDS.…”

T-Cell Large Granular Lymphocyte Leukemia and Related Disorders

“…Saunthararajah et al described nine patients who had myelodysplastic features in their bone marrow (either a clonal karyotype, megakaryocytic dysplasia and/or myeloid dysplasia, and/or >15% ringed sideroblasts) and a clonal expansion of LGLs [54]. Three of those patients responded to immunosuppression, with improvements in their blood counts.…”